Introduction

Uses for Insulin Lispro

Diabetes Mellitus

Used to control hyperglycemia in the management of diabetes mellitus.12361247757778

In patients with type 1 diabetes mellitus, generally used in conjunction with an intermediate-acting or long-acting insulin preparation (i.e., isophane [NPH] insulin human, insulin lispro protamine [as the fixed combination Humalog Mix 75/25], insulin zinc [Lente], extended insulin human zinc [Ultralente]), to provide prandial glycemic control.17374767778798196144145159160161165 In patients with type 2 diabetes mellitus, may be used without a longer-acting insulin when given with a sulfonylurea agent.1158159160161165

Slideshow: Newly Approved Weight Loss Drugs - Can They Help You?

Patients likely to benefit from insulin lispro therapy include type 1 diabetics who desire a more flexible injection schedule, those with low glycosylated hemoglobin values, and patients with recent-onset type 1 diabetes mellitus who have some residual β-cell function to provide basal insulin levels between meals.61256597477787981144145

The effects of age, obesity, gender, and type of diabetes mellitus on glycemic response do not appear to differ in patients receiving insulin lispro versus insulin human.151

Some clinicians suggest that patients who are well-controlled on conventional short-acting insulin preparations without frequent hypoglycemia should not be routinely switched to insulin lispro.74144

Insulin Lispro Dosage and Administration

General

Insulin lispro and insulin human are equipotent on a unit-for-unit basis with regard to glucose-lowering activity.123791219475159

Any change in insulin should be made cautiously and only under medical supervision.1 Changes in insulin strength, manufacturer, type (e.g., regular, NPH), species (animal, human), or method of manufacture (rDNA versus animal-source insulin) may necessitate a change in dosage.1

Transferring from Therapy with Other Insulins

Make any change in insulin preparation or dosage regimen with caution and only under medical supervision.11951

Not possible to clearly identify which patients will require a change in dosage when therapy with a different preparation is initiated.69121951

When switching from insulin human (regular) in regimens consisting of multiple insulin doses, use the previous insulin (regular) dosage as the initial dosage of insulin lispro.17274147 Subsequent dosage adjustments may be required due to changes in insulin purity, strength, brand, type, species source, or method of manufacture.123791219475159 Adjustments may be needed with the first dose or over a period of several weeks.1

When switching from insulin human (regular) in combination with a longer-acting insulin, dosage adjustment of the longer-acting insulin may be required.1125158757778147154

Patients receiving intensive insulin therapy (≥3 insulin injections daily with dosage adjusted according to results of at least 4 daily blood glucose determinations, dietary intake, and anticipated exercise) will achieve greater postprandial glycemic control than those receiving conventional therapy because of the increased use of rapid- or short-acting insulin.692259

Patients who previously were inadequately controlled on conventional insulin therapy generally will require a smaller total daily insulin dosage when switched to an intensive insulin regimen.692259

Administration

Do not administer insulin lispro in fixed combination with insulin lispro protamine IV.a

To improve accuracy of dosing in pediatric patients, may be diluted to a ratio of 1:10 or 1:2 with the sterile diluent supplied by the manufacturer.1

Sub-Q Injection

For solution and drug compatibility information, see Compatibility under Stability.

Administer by sub-Q injection immediately (i.e., within 15 minutes before or after a meal) using a conventional insulin syringe or an injection pen (e.g., Becton-Dickinson [B-D] Pen, Humalog Pen, Novo Nordisk’s NovoPen).119155156157

Generally administered in multiple daily doses in regimens that also include an intermediate- or long-acting insulin (e.g., NPH, Lente, Ultralente) given in the morning and/or evening to provide basal insulin needs.17274

Dosage

Pediatric Patients

Diabetes Mellitus

Sub-Q Injection

Individualize dosage; adjust dosage regularly based on blood glucose determinations.1n Usually, the total daily insulin requirement in children with type 1 diabetes mellitus ranges from 0.2–1 units/kg (generally 0.5–0.8 units/kg daily).222847z Adolescents in a growth phase may require an initial insulin dosage of 1–1.5 units/kg daily.28 No specific dosage recommendations by manufacturer.1 When used as a preprandial treatment regimen in clinical trials, 26–64% of total insulin requirements have been provided by insulin lispro, with the remainder provided by an intermediate-acting or long-acting insulin.noqtu

Sub-Q Infusion

No specific dosage recommendations by manufacturer.1 In a clinical trial, preprandial administration of insulin lispro injection comprised approximately 66% of the total daily insulin dosage, with the remainder given as a basal infusion.q

Adults

Diabetes Mellitus

Sub-Q Injection

Individualize dosage; adjust dosage regularly based on blood glucose determinations.1 Usually, the total daily insulin requirements in patients with type 1 diabetes mellitus is 0.5–1 unit/kg.h No specific dosage recommendations by manufacturer.1 When used in a preprandial treatment regimen in clinical trials, 39–66% of total insulin requirements have been provided by insulin lispro, with the remainder provided by an intermediate-acting or long-acting insulin.147ijklr

In patients with type 2 diabetes mellitus who are not controlled on intermediate-acting or long-acting insulin, some clinicians suggest initiating preprandial therapy with a short-acting or rapid-acting insulin, with the preprandial injection comprising 40–50% of the total insulin dosage.p

Sub-Q Infusion

No specific dosage recommendations by the manufacturer.1 In patients with type 1 diabetes mellitus, preprandial administration of insulin lispro injection has been used in clinical trials, comprising approximately 21–46% of the total daily insulin dosage, with the remainder given as a basal infusion.168mrs

No specific dosage recommendations by the manufacturer.a Initially, 0.3–0.5 units/kg daily given in 2 divided doses (before morning and evening meal) has been used in patients with type 2 diabetes mellitus.vy Subsequent dosage has been titrated in increments of 2–4 units per injection per day every 2–3 days to achieve the targeted fasting blood glucose concentration.vy Mean daily maintenance insulin dosage achieved was 0.46–0.66 units/kg.159vwxy

Hypoglycemia

Care should be taken in patients who are most at risk for the development of these effects, including patients who are fasting or those with defective counterregulatory responses (e.g., patients with autonomic neuropathy, adrenal or pituitary insufficiency, those receiving β-adrenergic blocking agents).

Rapid changes in serum glucose concentrations may precipitate manifestations of hypoglycemia, regardless of glucose concentrations.1 Homeostatic responses become defective, and early warning signs of hypoglycemia may be diminished or absent in patients with long-standing type 1 diabetes mellitus, diabetic neuropathy,1 and/or those receiving drugs such as β-adrenergic blocking agents that mask catecholamine-induced manifestations of hypoglycemia (e.g., tremors, palpitations).1

Use intensive insulin therapy with caution in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes. Higher target blood glucose concentrations (e.g., fasting blood glucose concentrations of 140 mg/dL and 2-hour postprandial concentrations of 200–250 mg/dL) are advisable in these patients.

Hypokalemia

Specific Populations

Pregnancy

Lactation

Not known whether insulin lispro is distributed into milk, however, other insulins (e.g., insulin human) are distributed into milk.11 Caution if used in nursing women.1 Adjustments in insulin lispro dosage and/or meal plans may be required.1

Pediatric Use

Safety and efficacy of insulin lispro in fixed combination with insulin lispro protamine not established in children <18 years of age.165

Insulin lispro has been used in children aged 3–18 years of age with type 1 diabetes mellitus,15174 and preliminary data suggest no unusual effects of insulin lispro therapy in adolescents receiving the drug.74118144145149150151 Adjustment of basal insulin dosages may be required.1

Geriatric Use

Safety of intensive insulin regimens in geriatric patients has been questioned. Increased incidence of hypoglycemia associated with intensive insulin therapy may increase the probability of strokes and heart attacks in such patients.

Hypoglycemic reactions may mimic a cerebrovascular accident.d Patients with type 2 diabetes mellitus may be more vulnerable to serious consequences of hypoglycemia (e.g., fainting, seizures, falls, stroke, silent ischemia, MI, or sudden death) due to an increased incidence of macrovascular disease.

Response in patients ≥65 years of age does not appear to differ from that in younger adults.1

Onset

Many factors can affect the onset, degree, and duration of insulin activity (e.g., injection technique, presence of insulin antibodies, site of injection, tissue blood supply, temperature, excipients in insulin formulations, and interindividual and intraindividual differences in response).119477483

Food

Special Populations

The presence of hepatic impairment does not affect the absorption in patients with type 2 diabetes mellitus.1

Distribution

Not known whether insulin lispro is distributed into human milk; however, other insulins (e.g., insulin human) are distributed into milk.1 Does not appear to cross the placenta in pregnant women with gestational diabetes.164

Extent

The volume of distribution of insulin lispro reportedly is identical to that of insulin human and ranges from 0.26–0.36 L/kg.1

Special Populations

Hepatic impairment does not affect the distribution in patients with type 2 diabetes mellitus.1

Elimination

Metabolic fate has not been determined in humans.1165 In animals, metabolism of insulin lispro is identical to that of insulin human.1165

Metabolism

Insulin is rapidly metabolized mainly in the liver and to a lesser extent in the kidneys and muscle tissue.d

Half-life

Special Populations

Circulating insulin concentrations may be increased in patients with renal or hepatic failure.1

Stability

Storage

Parenteral

Injection, for Sub-Q Use

With unopened vials, disposable injection pens, or cartridges of the drug that have not been placed in a delivery device, 2–8°C.119156165 Do not freeze; discard vial or cartridge if frozen.119156165

With vials, pens, or cartridges of insulin lispro that cannot be refrigerated or vials, cartridges, and disposable injection pens that are in use, <30°C for up to 28 days.1195181155 Protect from heat and light.1155

With disposable injection pens of insulin lispro in fixed combination with insulin lispro protamine (Humalog Mix 75/25 Pen) that are in use, room temperature for up to 10 days.160165 Protect from light and excessive heat.160165

When insulin lispro is diluted with the sterile diluent for pediatric use, discard the diluted solution after 28 days when stored at 5°C or after 14 days when stored at 30°C.165

Should not expose insulin lispro in the external infusion device to temperatures >37°C during administration.1 Replace infusion sets (reservoir syringe, tubing, and catheter), the DisetronicD-TRON or DisetronicD-TRONplus cartridge adapter, and insulin lispro in the pump reservoir and select a new infusion site at least every 48 hours.1 Should discard the 3-mL cartridges used in the DisetronicD-TRON or DisetronicD-TRONplus insulin pumps after 7 days, even if some drug still remains in the reservoir.1

Simulated administration of insulin lispro by continuous sub-Q infusion in several external infusion pump systems (i.e., Disetronic H-TRON, Minimed Model 504 pumps) revealed no changes in the potency, purity, or physical stability of the drug when stored within each of these devices for 48 hours.5181146163 However, precipitation of insulin lispro on infusion catheters (i.e., Silhouette, Soft-Set catheters) has been noted in several patients who were receiving insulin lispro via one of several external pump systems (i.e., Disetronic H-TRON V-100, Minimed 507C pumps).167

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

When insulin lispro is mixed with a longer-acting insulin preparation, insulin lispro should be drawn into the syringe first in order to prevent precipitation or turbidity of the insulin lispro solution by the longer-acting insulin.1 Insulin mixtures should not be administered IV.1

Should not dilute or mix insulin lispro with any other insulin when administered via an external sub-Q controlled-infusion device (pump).1

Drug Compatibility

Admixture Compatibility 1

Compatible

Extended human insulin zinc

Insulin, isophane human (recombinant DNA origin)

Actions

Facilitates cellular uptake of glucose in muscle and other tissues, except the brain.cd Stimulates protein synthesis and inhibits protein catabolism.1d

Inhibits output of glucose from the liver.9cd In the liver, insulin facilitates phosphorylation of glucose to glucose-6-phosphate which is converted to glycogen or further metabolized.d Promotes the conversion of excess glucose into fat.1

Importance of strict adherence to manufacturer’s instructions regarding assembly, administration, and care of specialized delivery systems, such as insulin pens.72144145e

Importance of changing insulin preparation or dosage with caution and only under medical supervision.11951 Discuss potential for alterations in insulin requirements and need for additional monitoring of blood glucose concentrations in special situations (e.g., illness, concomitant agents that alter glycemic control, travel, emotional disturbances, or other stresses).

Advise patients of the risks and advantages of conventional and intensive insulin therapy.

Importance of administering insulin lispro sub-Q within 15 minutes before or immediately after a meal.1

Advise patient not to smoke within 30 minutes after insulin injection, due to potential for decreased absorption of insulin.e

Importance of carefully advising patients of the differences in action profiles between insulin lispro and insulin human (regular) during transfer from insulin human to insulin lispro.174 May be necessary to adjust the consumption and/or timing of snacks or exercise to avoid hypoglycemic episodes and/or prevent preprandial hyperglycemia.174

Importance of regular self monitoring of blood glucose concentrations.1e Particular importance of frequent self monitoring of blood glucose concentrations in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes.

Importance of wearing a medical identification bracelet or pendant, carrying ample insulin supply and syringes on trips, and having carbohydrates (sugar or candy) on hand for emergency.e

Importance of not changing the order of mixing insulins or the model or brand of syringe or needle without medical supervision.1e When mixing with long-acting insulin preparations, importance of drawing insulin lispro into the syringe first.e

Importance of patients being aware of symptoms of diabetic ketoacidosis and the need to monitor blood ketones if preprandial blood glucose concentrations repeatedly exceed 250–300 mg/dL or if they have an acute illness. Importance of contacting a physician if results of self-monitored blood glucose concentrations are consistently abnormal.

Inform patient that use of marijuana may increase insulin requirements.e

Instruct patient on the appropriate measures for safe disposal of needles.e

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

21. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329:977-86. [IDIS 320201] [PubMed 8366922]

88. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997; 20:1183-97. [PubMed 9203460]

89. Diabetes Control and Complications Trial Research Group. Hypoglycemia in the diabetes control and complications trial. Diabetes. 1997; 46:271-86. [IDIS 380959] [PubMed 9000705]